Impact of age, prior therapies, and subsequent transplant on long-term outcomes of adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) treated with brexucabtagene autoleucel (brexu-cel) in ZUMA-3.
Authors: Bijal D. Shah, Ryan Daniel Cassaday, Jae H. Park, Roch Houot, Olalekan O. Oluwole, Aaron Logan, Nicolas Boissel, Thibaut Leguay, Michael Russell Bishop, Max S. Topp, Kristen M. O'Dwyer, Maria R. Baer, Gary J. Schiller, Mehrdad Abedi, Monique C. Minnema, Patrick J. Stiff, Lang Zhou, Tsveta Hadjivassileva, Rita Damico Khalid, Armin Ghobadi
Journal: Journal of Clinical Oncology (2023)

7023 Background: Brexu-cel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the US for adults with R/R B-ALL and in the EU for adults ≥26 y with R/R B-ALL based on positive results of ZUMA-3. After 3-y follow-up in ZUMA-3, brexu-cel demonstrated an overall complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate of 71% and a median overall survival (OS) of 26.0 mo in all treated pts (N = 55) and 38.9 mo in pts with CR (n = 31; Shah et al. EU CAR T 2023. Abstract 34). Here we report 3-y outcomes by age, prior therapies, and subsequent allogeneic stem cell transplant (alloSCT). Methods: Pts (≥18 y) had R/R B-ALL and received 1 brexu-cel infusion (1×10⁶ CAR T cells/kg) following leukapheresis and conditioning chemotherapy. The primary endpoint was overall CR/CRi rate per independent review. Post hoc subgroup analyses were exploratory, with descriptive statistics reported. Results: As of July 23, 2022, the median follow-up in Phase 2 (N = 55) was 38.8 mo (range, 32.7-44.6). The CR/CRi rate (95% CI) was 67% (35-90) for pts &lt; 26 y (n = 12) and 72% (56-85) for pts ≥26 y (n = 43). The median (95% CI) OS was 28.6 mo (0.6-not estimable [NE]) for pts &lt; 26 y and 34.1 mo (15.9-NE) for pts ≥26 y. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 92% of pts &lt; 26 y and in 88% of pts ≥26 y. For pts with 1 prior therapy (n = 10), the CR/CRi rate was 90% (95% CI, 55-100) and for pts with ≥2 prior therapies (n = 45), the CR/CRi rate was 67% (95% CI, 51-80); medians (95% CI) for OS were not reached (NR; 2.1-NE) and 25.6 mo (14.2-38.9), respectively. The incidence of Grade ≥3 TRAEs was 90% for pts with 1 prior therapy and 89% for pts with ≥2 prior therapies. The CR/CRi rates (95% CI) for pts with (n = 25) and without (n = 30) prior blinatumomab (blina) were 60% (39-79) and 80% (61-92). The median (95% CI) OS was 14.2 mo (3.2-26.0) for pts with prior blina and NR (18.6-NE) for pts without prior blina; Grade ≥3 TRAEs occurred in 80% and 97% of pts, respectively. For responders (CR/CRi) who did (n = 10) or did not (n = 29) proceed to subsequent alloSCT, the median (95% CI) OS was NR (7.6-NE) and 38.9 mo (18.6-NE), respectively. Similar efficacy results were observed in a pooled subgroup analysis of Phase 1 and 2 pts treated at the pivotal dose (N = 78), with a median follow-up of 41.6 mo (range, 32.7-70.3). Conclusions: Adults with R/R B-ALL benefitted from brexu-cel, regardless of age, number of prior therapies, prior blina exposure, or subsequent alloSCT status. Survival appeared longer in pts with fewer prior therapies and in blina-naïve pts; however, small pt numbers and unmatched baseline characteristics limit interpretation of these results. Additional studies are needed to determine the impact of prior therapies and/or subsequent alloSCT on outcomes of pts who receive brexu-cel. Clinical trial information: NCT02614066 .